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Biomedical subjects

Michel Huguier

Publications and source records attributed to Michel Huguier.

17 recordsLinked to original sources

Colon cancer prognosis prediction by gene expression profiling.

This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in stage II and III colon cancer patients. Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (nine with a recurrence, nine with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbour method was used for prognosis prediction using T and NM gene expression measures. Six-fold cross-validation was applied to select the number of neighbours and the number of informative genes to include in the predictors. Based on this information, one T-based and one NM-based predictor were proposed and their accuracies were estimated by double cross-validation. In six-fold cross-validation, the lowest numbers of informative genes giving the lowest numbers of false predictions (two out of 18) were 30 and 70 with the T and NM gene expression measures, respectively. A 30-gene T-based predictor and a 70-gene NM-based predictor were then built, with estimated accuracies of 78 and 83%, respectively. This study suggests that one can build an accurate prognosis predictor for stage II and III colon cancer patients, based on gene expression measures, and one can use either tumour or non-neoplastic mucosa for this purpose.

Adenocarcinoma↗

Gene expression profiling of nonneoplastic mucosa may predict clinical outcome of colon cancer patients.

PURPOSE: This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in Stage II and III colon cancer patients. METHODS: Tumor and nonneoplastic mucosa mRNA samples from 12 colon cancer patients were profiled using the Affymetrix HGU133A GeneChip. Six of 12 patients experienced a metachronous metastasis, whereas the 6 others remained disease-free for more than five years. Three datasets were constituted, including, respectively, the gene expression measures in tumor samples (T), in adjacent nonneoplastic mucosa samples (A), and the log-ratio of the gene expression measures (L). The step-down procedure of Westfall and Young and the k-nearest neighbor class prediction method were applied on T, A, and L. Leave-one-out cross-validation was used to estimate the generalization error of predictors based on different numbers of genes and neighbors. RESULTS: The most frequent results were one false prediction with the A-based predictors (95 percent) and two false predictions with the T- and L: -based predictors (65 and 60 percent, respectively). A-based predictors were more stable (i.e., less sensitive to changes of parameters, such as numbers of genes and neighbors) than T- and L: -based predictors. Informative genes in A-based predictors included genes involved in the oxidative and phosphorylative mitochondrial metabolism and genes involved in cell-signaling pathways and their receptors. CONCLUSIONS: This study suggests that one can build a prognosis predictor for Stage II and III colon cancer patients, based on microarray gene expression measures, and suggests the potential usefulness of nonneoplastic mucosa for this purpose.

Aged↗

Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy of adjuvant chemotherapy on survival after resection for gastric cancer. METHODS: Patients were enrolled if they underwent resection of gastric cancer but had lymph node or serosal involvement or both. Surgical resection was either total or partial gastrectomy according to the site of the tumor, and surgeons were allowed to perform either D1 or D2 gastrectomy. The subjects were random assigned in two treatment groups as follows: surgery alone as the control group, or surgery and adjuvant chemotherapy. Nine cycles of 5 days protocol every 4 weeks was proposed to the patients of the chemotherapy group. The protocol included a daily administration of 200 mg/m(2) of folinic acid, 5-fluorouracil (375 mg/m(2) during the first session increasing 25 mg by session until reaching 500 mg/m(2)) and CDDP 15 mg/m(2). Two hundred patients were required. Kaplan-Meier survival curves were compared according to the log-rank and the Mantel-Haenszel methods. RESULTS: In all, 205 patients were enrolled in the study; 104 had surgery alone and 101 had surgery and adjuvant chemotherapy. The patients' characteristics were similar except for the mean age, which was 4 years less in the control group. Because of toxicity, 54% of the patients stopped the protocol before the end of the nine courses, and 46% of the patients received the nine courses including 32% with a decreased dose and 14% with a full dose. The 5-year survival rate was 39% in the control group and 39% in the chemotherapy group. CONCLUSIONS: This protocol of adjuvant chemotherapy failed to improve the 5-year survival after resection for gastric cancer.

Adult↗

[Research and surgery. French experiences].

Clinical research in surgery often involves multicenter randomised studies. French associations for surgical research, created in the 1980s, have promoted an increase in the French contribution to international clinical research. According to a ten-year audit of randomised trials, France was the second European country (after the UK) for the number of published trials. Basic research in surgery was stimulated by the creation of a specific diploma (Diplôme d'études approfondies de sciences chirurgicales). It gives young surgeons the opportunity to be trained in basic research during a full-time one-year course in a laboratory. Some laureates carry on their research to PhD level. From 1986 to 2001, 611 students received the Diploma.

Biomedical Research↗

[Evidence based surgery of cancer of head of pancreas].

Physicians and surgeons who treat patients with gastrointestinal or hepatic disease must prescribe the most appropriate diagnostic tests, together with an accurate prognosis and effective and safe therapy. This paper examines the best modalities of surgical treatment for cancer of the pancreas, in an evidence-based approach. Evidence was classified as follows: Grade A : evidence from large randomized controlled trials (RCT) or systematic reviews (including meta-analyses) of multiple randomized trials which collectively have at least as much data as one single well-defined trial. Grade B: evidence from at least one high-quality study of non-randomized cohorts or evidence from at least one high-quality case-control study or one high-quality case series. Grade C: opinions from experts without references or access to any of the foregoing The data were obtained from Medline and from controlled randomized trials listed in the Cochrane Library up to the end of 2003. Two series (grade B) showed the superiority of Whipple over total pancreatectomy, with respective median survival times of 12.6 months and 9.6 months. Extensive lymphadenectomy (grade A) in patients with positive lymph nodes gave significantly better survival than standard resection in one trial, but this was not confirmed in the other trial. Results of pylorus-preserving pancreaticoduodenectomy (PPPD) were not different from those of the Whipple procedure on postoperative mortality, morbidity or survival (grade A). Portal vein resection increased the resectability rate. Post-operative mortality was not increased: survival was not different in four studies and was shorter in another four studies (grade C). Low-dose postoperative erythromycin accelerates gastric emptying if the right gastric artery is preserved (grade A). One trial suggests that pancreaticogastrostomy reduces the risk of pancreatic fistula. The two other trials are controversial and showed no difference. One prospective non randomized study showed that stenting in pancreaticojejunostomy reduces the risk of pancreatic fistulae and intraabdominal abscess. To prevent this risk of pancreatic fistula, six controlled trials involving patients receiving octreotride were performed Three European trials showed a smaller volume of abdominal drainage fluid and an abnormal amylase concentration; however, two American trials failed to demonstrate a significant difference. Occlusion of the pancreatic duct with fibrin glue did not reduce the risk of pancreatic fistula, but increased the risk of developing diabetes. Intraabdominal drainage after pancreatic resection significantly increased post-operative complications (grade A). Surgical resection and reconstruction procedures for pancreatic cancer must be based on evidence-based studies. However, the most important prognostic factor is the surgeon's experience, not only with regard to the post-operative course, but also survival. Specific teaching and training is thus essential.

Evidence-Based Medicine↗

Rectal cancer surgery in patients more than 80 years of age.

BACKGROUND: This retrospective study aimed to compare the prognosis for rectal cancer in patients more than 80 years old with that observed in younger patients. METHODS: Patients operated on for a rectal adenocarcinoma, from 1980 to 1998, were divided into two groups: group 1 (>80 years, n = 92); group 2 (<80 years, n = 276). RESULTS: There were significant differences between the two groups with regard to the sex ratio, the American Society of Anesthesiologists (ASA) classification, the emergency presentation, and the curative operation rate. The operative mortality rate was 8% in group 1, 4% in group 2 (P = 0.26). The overall 5-year survival rate was 35% in group 1, 53% in group 2 (P = 0.0004). In patients operated on for cure, the cancer-specific 5-year survival rate was 50% in group 1, 59% in group 2 (P = 0.08). CONCLUSIONS: The prognosis for rectal cancer in patients over 80 years is not significantly different from that of younger patients. Surgery should not be restricted on the basis of age.

Adenocarcinoma↗

Early gastric carcinoma: spread and multicentricity.

BACKGROUND: In early gastric carcinoma (EGC), after subtotal gastrectomy, recurrent lesions limited to the gastric remnant are the cause of about 20% of deaths from recurrence. Therefore, it has been suggested to perform total gastrectomy in all cases of EGC. METHODS: We studied a case series of 82 consecutive patients operated on for an EGC, with a mean follow-up time of 72 months (range, 1-120 months). Subtotal distal gastrectomy was performed 61 patients, total gastrectomy in 15, and other procedures in 6. Outcome measures were recurrence and causes of mortality, focusing on patients with resection line involvement and multifocal lesions. RESULTS: EGC was limited to the mucosa in 43 patients and had invaded the submucosa in 39. Ten patients had a lymph node involvement. In 4 patients having had a subtotal gastrectomy, resection line involvement was detected. In 3 patients, the involvement was detected peroperatively on frozen sections, and a re-resection was performed. In the fourth patient, the involvement was detected postoperatively, but follow-up endoscopies failed to show any residual tumor. In 17 patients, multifocal lesions were observed. No recurrence was observed in the gastric remnant of patients having undergone a subtotal gastrectomy. CONCLUSION: In distal EGC, a subtotal gastrectomy may be performed under two conditions: (1) careful endoscopic and peroperative examination of the upper part of the stomach to detect multifocal lesions and (2) a systematic frozen-section assessment of the resection margin to avoid inadequate resection.

Adult↗

[18 F-fluorodeoxyglucose positron emission tomography for characterization and initial staging of pancreatic tumors].

AIM: To evaluate positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) for characterizing and initial staging of pancreatic tumors and to determine its impact on therapeutic strategy. PATIENTS AND METHODS: This study included 24 patients with pancreatic tumor who underwent PET before treatment. Twenty-two patients had a malignant tumor and two had a benign tumor. The PET scan was performed after intravenous injection of FDG with a gamma camera. PET findings were compared with histology of the pancreatic tumor (n=24), liver metastases (n=5), peritoneal metastases (n=5), and lymph node metastases (n=5). Absence of metastasis or lymph node involvement was determined by surgery or by CT scan, ultrasonography, magnetic resonance imaging and at least two months follow-up. RESULTS: The sensitivity of the PET scans to identify pancreatic carcinoma was 64% (95% confidence interval 44-84%). PET scans could not be interpreted for lymph node involvement adjacent to the tumor. For liver metastases, the PET scan was positive in 3 out of 5 patients. For peritoneal metastases, the PET scan was positive in 4 out of 5 patients but was doubtful in one. There were two false positives. Among the 4 cystic tumors, the PET scan was positive for 2 malignant tumors and negative for 2 benign tumors. Surgical strategy was modified in only one of the 24 patients on the basis of PET findings. CONCLUSION: The sensitivity of PET for the diagnosis of primary malignant pancreatic tumor was found to be low. The contribution of FDG-PET to the surgical decision appears to be limited to the detection of metastases or lymph node involvement distant from the tumor, contraindicating surgery. Nevertheless, the sensitivity of FDG-PET is lower than that of laparoscopy for peritoneal metastases. Indications for PET should be included in an evaluation of therapeutic decision making and cost analysis.

Adult↗

Cardio-esophageal cancer. Is 18Fluorodeoxyglucose positron emission tomography worthwhile?

BACKGROUND/AIMS: 18Fluorodeoxyglucose positron emission tomography has been proposed for the preoperative staging of carcinomas of the esophagus and gastric cardia. The aim of this study was to assess its diagnostic value and its influence on therapeutical decisions. METHODOLOGY: Twenty-eight patients with a cancer of the esophagus or gastric cardia underwent a 18Fluorodeoxyglucose positron emission tomography on a gamma camera with coincidence detection electronics, in addition to our standard preoperative procedures (barium swallow, liver ultrasonography, chest X-ray). Four types of lesions were searched for: primary tumor, abdominal and mediastinal lymph nodes, and distant metastases. Results of 18Fluorodeoxyglucose positron emission tomography were compared to pathological findings. RESULTS: Sensitivity for the primary tumor was 86%. Sensitivity for mediastinal and abdominal lymph nodes was 75 and 54%, respectively, whereas specificity was 100%. Distant metastases were detected in 4 patients: liver metastasis in 2 patients and bone metastasis in 2 patients. Results of 18Fluorodeoxyglucose positron emission tomography influenced therapeutical decisions for 2 patients. CONCLUSIONS: 18Fluorodeoxyglucose positron emission tomography seems to be worthwhile in the preoperative staging of carcinomas of the esophagus and gastric cardia, mainly because it may detect distant metastases.

Aged↗